Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Abstract

Multiple sclerosis (MS) is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and experimental autoimmune encephalomyelitis (EAE). The curation of this literature has identified that central nervous system (CNS) infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

“…LTo cells also begin to express intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in order to aid in immune cell retention upon entry. Finally, LTo cells will differentiate into FDCs, fibroblastic reticular cells (FRCs), and marginal reticular cells, which comprise the stromal reticular network ( 89 , 91 , 92 ).…”

“…Partially due to their formation being initiated by inflammation, eLFs can form and dissipate quickly. As a direct consequence of this transient nature, eLFs can display significant organizational and cellular heterogeneity ranging from small and disorganized aggregates of B and T cells to highly organized structures containing compartmentalized T and B cell zones, HEVs, FDCs, and a developed stromal reticular network ( 10 , 11 , 80 , 90 , 91 ). It is important to note, however, that once the reticular network has formed and an eLF has reached an advanced state of maturation, eLFs become fairly stable and are less likely to dissipate ( 94 ).…”

“…Importantly, these samples are typically obtained at later stages of disease when inflammation is possibly less pronounced ( 89 ). Therefore, while heterogeneous observations between patients regarding cellular composition and structural organization can partly be explained by the transient nature of eLFs, it is more likely a consequence of differences in disease stage and varying degrees of residual CNS inflammation between patients ( 91 ).…”

The direct deleterious effect of Th17 cells in the nervous system compartment in multiple sclerosis and experimental autoimmune encephalomyelitis: one possible link between neuroinflammation and neurodegeneration

“…In vitro assays showed that the B cells from MS patients display the capacity of coordinating Th17 riposte against neuro-antigens (30). As a result, in 2018 Quinn and Axtell described an 'inflammatory axis' consisting of Th17 cells, B cells and follicular Th cells (31). Th17 cells through their implication in the formation of the subpial follicles, have a contributory role in the underlying subpial grey matter pathology (4).…”

Coupling the Paternò-Büchi (PB) Reaction With Mass Spectrometry to Study Unsaturated Fatty Acids in Mouse Model of Multiple Sclerosis

“…To date, the experimental autoimmune encephalomyelitis (EAE) animal model best mimics the clinical and pathological hallmarks of multiple sclerosis and can offer the essential predictive guide for clinical therapeutic application (Miller and Karpus, 2007; Quinn and Axtell, 2018). Significantly elevated concentrations of acrolein, an α, α-unsaturated aldehyde and a reactive product of lipid peroxidation, has been found after rat spinal cord contusion injury.…”